PROTEIN: IS THE RECOMMENDED INTAKE ENOUGH?

How much protein should we consume per day? What is the Recommended Daily Intake of protein, is it really enough and most importantly, what are the negative health effects of protein overconsumption?

Many arguments about protein consumption requirements and adequacy are based on the premise that the Recommended Daily Intake recommendations are accurate and that they are a target that the general population should aim for, as they represent a level beyond which no additional benefit can be observed.

But exactly how concrete are these arguments, and more importantly, what really is the protein target we should aim for to avoid health problems?

THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN

The Recommended Daily Allowance (RDA) represents the estimated average requirement plus 2 standard deviations, i.e. it is intended to cover minimum protein needs for 97.5% of the healthy population, with protein needs being based on defining the safe upper limits.

This meta-analysis used 58 nitrogen balance studies in adults for the purpose of estimating the protein requirement of healthy adults, of which, the analysis for determining the Recommended Daily Allowance was finally restricted to 19 studies.

A simple linear regression model was employed to identify the point of zero balance. Use of this approach resulted in an Estimated Average Requirement (EAR) and Recommended Daily Allowance of 0.66g and 0.83g protein/kg body weight/day, respectively, for adults.

The Recommended Daily Allowance rounded down to 0.8 g/kg body weight/day was utilized by the U.S. Institute of Medicine to derive the Dietary Reference Intakes (DRI) for protein in 2005 and for the recommendations of the WHO/FAO report on protein and amino acid intake recommendations in 2007.

THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN IS BASED ON INCORRECT ANALYSIS

But metabolic adaptation to protein intake complicates the interpretation of nitrogen balance data.

Research on lysine requirements has demonstrated that the relationship between lysine intake and nitrogen balance is curvilinear, as the efficiency of protein utilization decreases as zero nitrogen balance is neared, which means that statistical models need to account for this nonlinearity.

A re-analysis of the published nitrogen balance data using the more appropriate, biphase linear regression model, resulted in a mean requirement of 0.91g protein per kg body weight per day and and a population-safe requirement estimate of 0.99g protein per kg body weight per day.

Diet, Diet, Health, Protein, Health, Longevity, Nutrition
Re-analysis of the published nitrogen balance data using a biphase linear regression model results in a Recommended Daily Allowance of 0.99g protein per kg body weight per day. Source: Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr. 2007 Oct;86(4):995-1002. doi: 10.1093/ajcn/86.4.995. PMID: 17921376.

Thus, the use of the two-phase regression analysis results in protein requirement estimates that are close to 25% higher than when simple linear regression is applied.

THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN HAS BEEN CALCULATED USING OUTDATED METHODS

Even though the nitrogen balance technique is not a tracer method, it has been considered the gold standard for close to 100 years and is the basis for current nutritional guidelines.

However, even though the nitrogen balance method can a useful tool, it is not without its difficulties and limitations.

The theory underlying the nitrogen balance method proposes that the amount of nitrogen consumption required to balance the amount of nitrogen lost from the body represents the amount of dietary nitrogen intake needed to maintain lean body mass.

Nitrogen balance analysis conventionally uses urinary nitrogen excretion to represent nitrogen loss from the body, but nitrogen can be lost by other routes, including feces, sweat and wound exudates, which means that errors toward positive nitrogen balance due to overestimation of dietary nitrogen intake and underestimation of nitrogen losses from the body are highly likely when using this method, as the net result leads to an overly positive balance and therefore an underestimation of the requirement.

The above has led to nitrogen balance studies in adults consistently displaying positive balances, with considerable apparent retention of nitrogen, which is biologically implausible.

The evidence on whole-body protein turnover strongly suggests that the components of protein turnover (breakdown and synthesis), including amino acid oxidation, are influenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role.

Diet, Diet, Health, Protein, Health, Longevity, Nutrition
Hypothetical model of effect of amino acid concentration on rates of protein synthesis (S) and breakdown (B) and the modulating effect of insulin. Balance occurs at the point where the curves cross. Dotted lines slow the effects of insulin, which shifts the curves to the left, to produce the increase in sensitivity. Synthesis is only moderately sensitive to amino acid concentration, breakdown more so. Source: Waterlow JC. the mysteries of nitrogen balance. nutr Res Rev. 1999 Jun;12(1):25-54. doi: 10.1079/095442299108728857. PMID: 19087445.

In other words, dietary energy and carbohydrate intake can alter the utilization of amino acids for energy which in turn means that nitrogen balance can also be affected by these factors.

Evidence of alternative roles of amino acids beyond their role as subunits of protein synthesis, as for instance in neurotransmission, indicate that a competitive scenario for the available amino acid pool could likely impact the homeostasis measured in a nitrogen balance study.

The above limitations are further supported by studies that have shown that the nitrogen balance is not equivalent to amino acid balance.

Finally, there are considerations that render nitrogen balance impractical. Long periods of adaptation are required to equilibrate the body’s nitrogen pool: a minimum of 3 days is needed per level of test intake and 7–10 days of adaptation are needed to each intake of protein or amino acid.

These considerations have led to alternative approaches to understanding protein needs.

BETTER METHODS AND APPROACHES IN UNDERSTANDING PROTEIN NEEDS

In the latest US Institute of Medicine Dietary Reference Intakes for protein as well as in the WHO/FAO report on protein and amino acid intake recommendations, it is acknowledged that, when performed over a 24-hour period for estimating amino acid requirements, the indicator amino acid oxidation approach is probably the most satisfactory method on theoretical grounds, representing the current state of the art, and that it is the chosen method for estimated amino acid requirements where data are available.

The indicator amino acid oxidation method is based on the premise that when one indispensible amino acid is deficient, all other amino acids (including a tracer-labeled indicator amino acid) will be oxidized. As the intake of the deficient or limiting amino acid increases, the rate of oxidation of the other amino acids will decline as more amino acids are incorporated into protein.

Even though the indicator amino acid method is not without its own flaws, it would at least be interesting to see what the Recommended Daily Allowance would be if this method were to be employed instead of the nitrogen balance method, since the former addresses many of the limitations of the latter.

THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN USING BETTER METHODS

In the same study that performed the reanalysis of the published nitrogen balance data using two-phase regression analysis, the authors also used the indicator amino acid technique to determine protein requirements in healthy adults.

Findings supported a mean requirement of 0.93g of protein per kg body weight per day, and a population-safe requirement estimate of 1.2g protein per kg body weight per day.

Diet, Diet, Health, Protein, Health, Longevity, Nutrition
Using the indicator amino acid oxidation (IAAO) method to determine protein requirements in healthy adults results in a Recommended Daily Allowance of 1.2g of protein per kg body weight per day. Source: Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr. 2007 Oct;86(4):995-1002. doi: 10.1093/ajcn/86.4.995. PMID: 17921376.

These values are approximately 1.5 times higher than the corresponding values published in the latest US Institute of Medicine Dietary Reference Intakes for protein and the WHO/FAO report on protein and amino acid intake recommendations.

Confirming the above, a recent study was conducted in young Chinese women using intact protein and meal feeding which applied the indicator amino acid oxidation method to determine protein requirements.

The results obtained for mean and population safe protein requirement were 0.91g and 1.09g per kg body weight per day, which are comparable to the estimates in the aforementioned study that used the indicator amino acid oxidation method.

RECOMMENDED DAILY INTAKE DOES NOT MEAN OPTIMAL INTAKE

Although the indicator amino acid oxidation method addresses many of the limitations of nitrogen balance, it still targets amino acid oxidation as an undesired metabolic outcome. Not only there is no evidence that efficiency equates to optimum metabolic health for adults, desirable metabolic outcomes can be expected as a result of amino acids being consumed in amounts greater than the requirements predicted from the nitrogen balance or indicator amino acid methods.

Dietary guidelines based solely on the efficiency of amino acid use for growth or nitrogen balance outcomes may be neglecting the fact that changes in intracellular amino acid concentrations and oxidative catabolism are an important means to regulate and support many normal metabolic responses beyond the synthesis of nitrogen-containing compounds.

Furthermore, research suggests that there may be a distinction between the minimal protein requirement (i.e. the Recommended Daily Allowance) and what is optimal to ensure long-term health, including the prevention of sarcopenia.

POPULATION GROUPS WITH HIGHER PROTEIN NEEDS

Even though both the US Institute of Medicine's latest Dietary Reference Intakes for protein and the WHO/FAO report on protein and amino acid intake recommendations do acknowledge special considerations for certain populations, the Recommended Daily Allowance is often considered a blanket statement and these considerations are overlooked.

New studies support increased needs for both total protein and certain amino acids for certain populations.

Populations whose protein needs are impacted by special metabolic demands include the older adults, young children, physically active adults, athletes in strength sports and athletes in endurance sports, pregnant and lactating women and individuals recovering from severe illness or trauma.

THE NEGATIVE EFFECTS OF PROTEIN ON HEALTH

Research has clearly shown that protein intakes higher than the Recommended Daily Allowance are not associated with detriments in health in healthy humans in healthy people.

But for the sake of argument, let's examine what theory suggests.

In a investigation of the fate of protein nitrogen, scientists were able to quantify the temporary accumulation of urea in body water during the peak rate of urea excretion and the amount hydrolysed in the gastrointestinal tract. An algorithm was then developed to estimate the liver's ability to amino acid amino acid aminogenesis and urea production, called the maximum rate of urea synthesis.

They found that the maximum rate of urea excretion in healthy subjects was 55 mg urea N per hour per kg3/4, which is achieved at an intake level of 0.53g of protein N per hour per kg3/4, while at higher protein intakes there is no further increase in urea excretion rate, but a prolongation of the duration of maximal rate of urea excretion, often in excess of 24 hours.

In the study, the maximum urea excretion rate averaged 65 mg urea N per hour per kg3/4 (with a range of 55 to 76) in healthy individuals, suggesting that the level of dietary protein that can be deaminated and processed through to urea by the liver in a 24 hour period is dependent on body weight and individual variation in efficiency of the process.

An 80 kg individual, for instance, could deaminate up to 301 g protein per day, but may be limited to 221 g protein per day, given the range in maximal rate of urea excretion determined by these data.

However, the safe intake level of protein consumption should actually be slightly higher than these figures, as not all protein is deaminated and converted to urea.

In other words, the protein that is used directly for structural/functional purposes, including bone and soft tissue growth, maintenance and repair plus production of hormones, antibodies, and enzymes, (i.e. the Recommended Daily Allowance) does not require deamination.

Diet, Diet, Health, Protein, Health, Longevity, Nutrition
The level of dietary protein that can be deaminated and processed through to urea by the liver in a 24 hour period, depending on body weight. Source: Bilsborough S, Mann N. A review of issues of dietary protein intake in humans. Int J Sport Nutr Exerc Metab. 2006 Apr;16(2):129-52. doi: 10.1123/ijsnem.16.2.129. PMID: 16779921.

Therefore, adding our protein requirements to the level of protein that can be converted to urea, yields a theoretical maximal daily protein intake based on body weight and efficiency of urea synthesis in individuals.

An 80 kg individual, for example, could theoretically tolerate 325 g protein per day (range 285 to 365 g) without showing symptoms of hyperammonemia and hyperaminoacidemia considering the Recommended Daily Allowance from nitrogen balance (as 0.8g of protein per kg of body weight per day yields 64g/day for an 80 kg person).

On the other hand, this same 80 kg individual, could theoretically tolerate 357g protein per day (range 317 to 397g) without showing symptoms of hyperammonemia and hyperaminoacidemia considering the Recommended Daily Allowance, as calculated by studies using the indicator amino acid oxidation method (1.2g protein per kg body weight per day yields 96g/day for an 80 kg person).

Taking our theoretical approach one step further, it should be noted that it may be wise to interpret these approximations with caution, since the rate of amino acid absorption from protein is usually quite slow when compared to that of other macronutrients.

For instance, whey isolate, which is considered to be one of the “fastest” known proteins, has an absorption rate of ~8-10 hours per gram, while the protein from cooked eggs needs about ~2.8 hours per gram to absorb. In comparison, 357g of protein would need an absorption rate of approximately 15 g/hour in order to be absorbed in one day.

Moving from theory to practice, the same institution that provided the Recommended Daily Allowance, the US Institute of Medicine, defines the Acceptable Macronutrient Distribution Range (AMDR) for protein to be 10% to 35% of total energy for adults.

Consequently, for an 80kg individual who requires 2600kcal of energy per day, the Acceptable Macronutrient Distribution Range for protein intake ranges anywhere from 0.8125g to 2.84375g/kg body weight/day for adults (that is, well above the Recommended Daily Allowance), or from 65g to 227.5g per day.

In summary:

  • The Recommended Daily Allowance is based on an outdated method with many shortcomings and uses an improper methodology to analyze the available data.
  • More recent methods suggest that the Recommended Daily Allowance needs to be around 1.2g per kg of bodyweight per day.
  • The Recommended Daily Allowance is intended to cover minimum protein needs for 97.5% of the healthy population and minimum does not necessarily mean optimal.
  • Special populations such as older adults, young children, physically active adults, strength and endurance athletes, pregnant and lactating women, and individuals recovering from severe illness or trauma probably require even more protein.
  • Increasing protein intakes well above the Recommended Daily Allowance can be safe, without leading to negative effects in healthy humans in theory or practice, and the range of protein recommendations from health authorities is quite wide.

-Suprastratum: The authority on health, fitness and nutrition

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Author: Nick Krontiris

Founder, Suprastratum

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